- The Food and Drug Administration on Tuesday released formal guidelines detailing the agency's standards for the emergency clearance of a coronavirus vaccine, prevailing over weeks of resistance from the White House, which had sought to make possible President Donald Trump's promises of an approval before the Nov. 3 election.
- Publication of the guidelines came just hours after the FDA disclosed key review criteria in a briefing document for an advisory panel meeting later this month, an apparent attempt to sidestep White House opposition to their publication as official guidance.
- The FDA had already communicated its standards to vaccine developers, which, through the drug lobby PhRMA, indicated their support of the guidelines in a public statement Tuesday. Polls have shown the U.S. public is concerned vaccine testing is being rushed, a perception the FDA has sought to remedy by committing to maintaining high standards for the safety and effectiveness of any would-be shot.
The weeklsong tug-of-war between the FDA and the White House over the agency's guidelines — normally a routine part of regulatory standard-setting — came to a head in less than 24 hours.
After both The New York Times and Politico reported Monday that White House officials had rejected the guidelines, the agency on Tuesday morning published a briefing document for an Oct. 22 meeting of its vaccine advisory committee. Contained within the document was an appendix spelling out efficacy and safety standards the FDA had already communicated to coronavirus vaccine developers regarding emergency authorization of an experimental shot.
The appendix effectively publicized the FDA's stance on early vaccine clearances without the formal release of a guidance document. Soon after, however, the White House reportedly dropped its objections and allowed the FDA to proceed anyway, which it did Tuesday afternoon.
The fight over what typically would be considered regulatory minutiae took on outsized importance due to concerns of political interference in the FDA's review process, worries which had become stronger after the regulator seemingly yielded to White House pressure by clearing hydroxychloroquine and convalescent plasma for emergency use.
"There are few moments that I could think of where so much political dust was kicked up for so little actual practical effect," said former FDA head Scott Gottlieb, now a member of Pfizer's board of directors, at an online event held by Johns Hopkins University and the University of Washington.
Reportedly at issue was the FDA's plans to require a median of two months of follow-up for participants in drugmakers' key vaccine trials. Doing so would allow for more data to be gathered in what has been a record sprint from laboratory tests to large-scale efficacy studies, potentially giving the FDA greater confidence in allowing early use of an experimental shot.
But the two-month bar would also make an emergency authorization before the Nov. 3 election all but impossible, irking the White House, according to reports.
The two month number was chosen as a target because many of the side effects the FDA might expect from a vaccine would likely emerge by then, said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, at the Johns Hopkins event.
For example, Guillain-Barre syndrome, a potential risk to certain vaccines, typically appears six weeks after inoculation, Marks said. Others like transverse myelitis, symptoms of which were reportedly observed in a study of AstraZeneca's vaccine, take closer to three months to show up.
At a median of two months, however, more than half of participants will have been followed for longer, allowing regulators to potentially see signals of some of the slower-developing adverse events.
"We picked two months as something that was reasonably aggressive, yet also somewhat in the middle, not too aggressive, not too conservative,” Marks said.
Pfizer appears the only vaccine developer that could possibly have early data soon enough to ask the FDA for an approval before the election. Some 37,000 people have been enrolled in its late-stage study to date, 28,000 of whom have received the second and final shot of their vaccination.
The drugmaker, though, likely won't have two months of follow-up on the median participant until mid-November, based on when the study started and how fast it enrolled.
The trial is designed to prove the vaccine's effectiveness (or lack of it) after 164 cases of COVID-19 have occured. But the independent committee overseeing the trial can look at the data four times before then, the first two of which can occur after 32 and 62 cases. Pfizer has indicated it expects to have data, likely from these early looks, by the end of October.
For the committee (and later, Pfizer) to declare success, the shot would need to be, respectively, at least 77% or 68% effective — a high bar to meet.
The FDA has said it will convene its advisory panel before each and every decision on an emergency vaccine authorization. The group is set to meet on Oct. 22 to discuss coronavirus vaccines broadly.
Moderna and AstraZeneca are close behind Pfizer, but Moderna's chief executive Stephane Bancel has said he doesn't expect to be in a position to ask for an early approval until late November. AstraZeneca's principal U.S. study, meanwhile, remains on hold due to safety concerns.
Ben Fidler contributed reporting.